Neither all anti-inflammatory drugs nor all doses are effective in accelerating the antidepressant-like effect of fluoxetine in an animal model of depression

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) have been studied as possible adjunctive therapy in the treatment of depression. However, administering NSAIDs to increase the effectiveness of antidepressant has yielded inconsistent results. Methods: We evaluated the effect of the co-administration of fluoxetine (5 mg/kg) and flurbiprofen (5 mg/kg) or fluoxetine (5 mg/kg) and celecoxib (5 mg/kg) in the chronic escape deficit (CED) model of depression after 7 days of treatment. The co-administration of fluoxetine plus acetylsalicylic acid (ASA, 45 mg/kg i.p.) was used as a positive control. Moreover, we tested the behavioral effect of different doses (45, 22.5, and 11.25 mg/Kg i.p.) of ASA as potentiating agent of the effect of fluoxetine in the same paradigm. Results: Our study showed that only the co-administration of ASA with fluoxetine was able to revert the stress induced condition of escape deficit after 7 days of treatment, and that the amplitude of the antidepressant-like effect of ASA was dose dependent. In the same experimental conditions, celecoxib with fluoxetine only partially resolved the stress-induced impaired behavior while flurbiprofen/fluoxetine cotreatment was ineffective. Limitations: Our study is still exploratory, more doses, longer treatment regimens, and different behavioral outcomes must be investigated to draw a clear conclusion. Conclusion: Our results further stress the importance of the type and dose when NSAIDs are associated with antidepressants to ameliorate a clinical response.